Gestational
Trophoblastic Disease
Current management
Background
Incidence –
U.S. and Europe 1/1500
South East Asia 1/150
(↓ Carotene, animal fat and Vit. A)
Can follow any gestational event – abortion, miscarriage, ectopic, normal
pregnancy
Curable in vast majority – chemotherapy 1956
Complete & partial mole
Invasive mole
Placental-site trophoblastic tumour
Choriocarcinoma ( always if follows term pregnancy 1/50,000 )
Latter 3 usually derive from molar pregnancy
Complete Mole
Pathology:
Generalized hydatidiform swelling and trophoblastic hyperplasia
fetal/embryonic tissue absent
Karyotype:
90% 46XX
haploid sperm fertilizes ovum and duplicates
ovum nucleus either absent or inactivated
10% 46XY
Clinical:
Diagnosis:
Vaginal bleeding
95%
Enlarged uterus
50%
Theca lutein cysts 50%
Hyperemesis
25%
PET
25%
Hyperthyroidism
5%
Trophoblastic emboli 2%
(prune juice, anaemia)
(often >6cm.- may take 3 months)
(no reported case of eclampsia)
(if free T4↑ - B-blockade)
U/S usually very sensitive – generalized swelling (snow-storm )
Complete Mole
Complete Mole Histology
Partial Mole
Triploid karyotype – extra haploid set paternal
Sometimes fetus present – usually triploid
Pathology differs from complete:
Clinical:
growth restricted / multiple anomalies
focal hydatidiform swelling
varying size of chorionic villi
marked villous scalloping
focal trophoblastic hyperplasia
identifiable embryonic or fetal tissues
Usually as a regular incomplete or missed abortion
Excessive uterine enlargement / PET very rare
No hyperemesis / hyperthyroidism / theca-lutein cysts
Diagnosis:
U/S may detect focal cystic spaces of varying diameter
Diagnosis on histology of curettings
Partial Mole Histology
Management
Pre-operative assessment – medical complications / CXR
Evacuation -
oxytocin infusion after curettage
heavy bleeding should not deter from cervical dilatation
suction curettage (fundal massage)
uterus usually dramatically reduces in size / bleeding controlled
complete with sharp curettage
Histological evaluation of all tissue
Natural history:
Complete - 15% local uterine invasion
4% metastatic disease
High risk - hCG > 100000
(40%)
large uterus
30% local invasion
theca lutein cysts > 6cm. 9% metastases
Partial mole -
4% local uterine persistence/no cases choriocarcinoma
Many centres have abandoned follow-up
Follow up
Weekly -hCG (syncytiotrophoblast)
levels until
normal for 3 consecutive weeks
Can take 12-14 weeks
Then monthly until normal
for 6 months
Contraception:
Immediate
Oral / barrier / permanent
No IUCD until hCG normal (perforation)
No  persistent disease on OCP and
regression time not influenced
GTN Follow-up
WHO Prognostic Scoring
Original assessment and scoring system 1984 changed in 2000
Metastatic disease occurs in 4% patients with molar pregnancy
Plateau: 4 values over 3 weeks
Rise:
 10% for 3 values over 2 weeks
Clinical examination – especially pelvis, vagina and vulva
U/S to exclude pregnancy
Brain – MRI superior to CT scan
Chest – CXR adequate for counting metastases / CT scan also acceptable
Abdomen – CT scan
WHO Prognostic Scoring
Prognostic factor
Age
Antecedent pregnancy
Interval (months)
Pre-treatment -hCG (log)
Largest tumour
Site of metastases
Number of metastases
Previous Chemo. Failed
Changes:
0
<39
Mole
4
<3
Prognostic score
1
>39
Abortion
4-6
<4
3-4
Spleen
Kidney
1-4
2
4
Term pregnancy
7-12
<5
>5
5
GI tract
Brain
Liver
5-8
>8
Single drug
2 or more
ABO group deleted, Liver mets score upgraded, no medium risk group
Low risk =  6
High risk =  7
 single agent chemotherapy
 combination chemotherapy
FIGO Staging
Stage 1
Tumour confined to uterus
Stage 2
Tumour confined to pelvis
Stage 3
Metastases to lung ( with/without pelvic metastases )
Stage 4
Distant organ metastases ( with/without lung metastases )
Chemotherapy
Low-risk
If non-metastatic - always curable
( Hysterectomy if chemo fails)
Methotrexate:
Many regimes
I.M. Methotrexate 1mg/Kg days 1,3,5,7
I.M./ P.O. Folinic acid 0.1mg/Kg days 2,4,6,8
I.M. Methotrexate 40mg/m² weekly
Actinomycin D:
I.V. push 1.25mg/m² every 14 days
Follow-up:
-hCG, FBC, LFTs and U/Es, creatinine prior to each cycle
Continue treatment cycle for 1-3 weeks after normal -hCG
Check -hCG monthly for 12 months, then 2 monthly for 12 months
Contraception for 12 months
Complete remission in 85-90%
80% require only one course
Toxicity: Thrombocytopenia 2%, neutropenia 6% and hepatotoxicity 14%
High Risk GTN
Invasive mole:
invades myometrium / diagnosed at hysterectomy / can metastasize
mets may be choriocarcinoma
Placental site trophoblastic tumour:
Locally invasive composed of cytotrophopblast
small if any rise in hCG (<3000)
vaginal bleeding usually after amenorrhoea
Large polypoid tumour / insensitive to chemotherapy
Curettage sometimes successful / Hysterectomy
Choriocarcinoma:
Accounts for majority of metastatic disease
Early vascular invasion and widespread dissemination
Fragile vessels  haemorrhagic complications
80% have lung mets – any respiratory symptom
30% have vaginal mets – highly vascular (avoid biopsy)
10% have liver mets – usually only with extensive tumour elsewhere
10% have brain mets – never isolated ( lung / vagina)
Treatment:
Prognosis:
EMA-CO chemotherapy +/- surgical resection / radiotherapy
75% complete response rate
Salvage chemo – BEP varying success
Pregnancy After GTN
No evidence of increased congenital anomalies after one year contraception
Recent Japanese data –
Women who concieved during follow-up period < 1 year
No adverse effect on anomalies nor preterm delivery
Risk of further molar pregnancy:
0.5-2.5% if one previous molar
33% if two previous molar
3 molar pregnancies – poor live birth rate
Risk of molar pregnancy increases with number of previous spontaneous abortions
Previous term pregnancies reduce risk of GTN
Conclusions
GTN is rare
Ultrasound diagnosis becoming more common
Senior staff should perform ERPC ( suction and sharp curettage)
Follow-up – clinical and serum -hCG measurements in specialized clinics
Chemotherapy curative in vast majority low risk patients